Expression of cell cycle regulators and frequency of TP53 mutations in high risk gastrointestinal stromal tumors prior to adjuvant imatinib treatment

Despite of multitude investigations no reliable prognostic immunohistochemical biomarkers in GIST have been established so far with added value to predict the recurrence risk of high risk GIST besides mitotic count, primary location and size. In this study, we analyzed the prognostic relevance of eight cell cycle and apoptosis modulators and of TP53 mutations for prognosis in GIST with high risk of recurrence prior to adjuvant treatment with imatinib. In total, 400 patients with high risk for GIST recurrence were randomly assigned for adjuvant imatinib either for one or for three years following laparotomy. 320 primary tumor samples with available tumor tissue were immunohistochemically analyzed prior to treatment for the expression of cell cycle regulators and apoptosis modulators cyclin D1, p21, p16, CDK4, E2F1, MDM2, p53 and p-RB1. TP53 mutational analysis was possible in 245 cases. A high expression of CDK4 was observed in 32.8% of all cases and was associated with a favorable recurrence free survival (RFS), whereas high expression of MDM2 (12.2%) or p53 (35.3%) was associated with a shorter RFS. These results were independent from the primary KIT or PDGFRA mutation. In GISTs with higher mitotic counts was a significantly increased expression of cyclin D1, p53 and E2F1. The expression of p16 and E2F1 significantly correlated to a non-gastric localization. Furthermore, we observed a significant higher expression of p21 and E2F1 in KIT mutant GISTs compared to PDGFRA mutant and wt GISTs. The overall frequency of TP53 mutations was low (n = 8; 3.5%) and could not be predicted by the immunohistochemical expression of p53. In summary, mutation analysis in TP53 plays a minor role in the subgroup of high-risk GIST before adjuvant treatment with imatinib. Strong expression of MDM2 and p53 correlated with a shorter recurrence free survival, whereas a strong expression of CDK4 correlated to a better recurrence free survival.Peer reviewe

Prolactin signaling and Stat5: going their own separate ways?

Miyoshi et al. compared the role of the prolactin receptor (PrlR) and its downstream mediator, the signal transducer and activator of transcription 5 (Stat5), in mammary epithelial cells in vivo by studying PrlR(-/-) and Stat5ab(-/-) mouse mammary epithelial transplants during pregnancy. At first glance, the two mutant epithelia appear to have similar defects in the differentiation of the alveolar epithelium. However, a closer examination by Miyoshi et al. revealed defects in the epithelial architecture of the smallest ducts of Stat5ab(-/-) transplants not apparent in the PrlR(-/-) transplants, suggesting that Stat5 is more than a simple mediator of PrlR action

Cognitive-behavioral therapy of school refusal: School phobia and school anxiety

Die Arbeit gibt einen Überblick über aktuelle kognitiv-verhaltenstherapeutische Behandlungsansätze nicht dissozialer Schulverweigerung (Schulphobie und Schulangst) bei Kindern und Jugendlichen. Einleitend wird der Problembereich definiert sowie der Stand des Wissens zu Prävalenz, Verlauf und Risikofaktoren dargestellt. Den Schwerpunkt der Arbeit stellt die psychotherapeutische Behandlung von Schulphobie und Schulangst dar. Neben allgemeinen Behandlungsprinzipien wird auf die wichtigsten verhaltenstherapeutischen Techniken sowie auf kognitivverhaltenstherapeutische Behandlungsprogramme eingegangen. Es folgt eine ausführliche Beschreibung des Stands der Wirksamkeitsforschung. Schließlich wird praxisnah der Ablauf der Diagnostik, Therapieplanung und -durchführung dargestellt.(DIPF/Orig.)The study provides an overview of current cognitive-behavioral interventions to treat school-refusal in children and adolescents. First of all we define the problem area and describe the standard of knowledge about prevalence, course and risk factors. The main focus of our work is presented by psychotherapeutic treatments of school phobia and school anxiety. Apart from general treatment principles we give a survey of the most important behavioral therapeutic as well as cognitive-behavioral therapeutic treatments. In addition, we provide a detailed description of current research about efficacy. After all we characterize diagnostic, treatment planning and implementation.(DIPF/Orig.

Depressionen im Kindes- und Jugendalter

Depressionen gehören zu den größten Gesundheitsproblemen weltweit. Auch im Kindes- und Jugendalter, insbesondere ab der Pubertät, treten sie häufig auf und können zu erheblichen psychosozialen Beeinträchtigungen und negativen Entwicklungsverläufen führen. Depressive Störungen zeigen sich bei Kindern und Jugendlichen im Einzelfall sehr unterschiedlich. Kernsymptome sind eine starke und anhaltende Traurigkeit oder Reizbarkeit, Antriebslosigkeit, eine reduzierte emotionale Schwingungsfähigkeit sowie der Verlust von Interesse und Freude. Der Entstehung einer Depression liegen unterschiedliche soziale, psychische und biologische Risiken und verschiedene Entwicklungswege zugrunde. Bei der Behandlung depressiver Störungen hat sich die Kognitive Verhaltenstherapie (KVT) als besonders wirksam erwiesen. Bei der KVT werden auf der Basis eines individuellen Störungsmodelles unter anderem Psychoedukation, Verhaltensaktivierung, kognitive Interventionen und die Förderung von Problemlösefertigkeiten und sozialen Kompetenzen in die Behandlung integriert. Der Umgang mit Suizidalität verdient in der Therapie eine besondere Beachtung

Trends in the composition of wet deposition: Effects of the atmospheric rehabilitation in East-Germany

The chemical components in precipitation largely depend on type and quantity of emissions on the course of the air masses at the sampling site. Beginning in 1982, the concentrations of major ions in precipitation at initially 3 sites are described in total as well as arrival sectors. For regions with specific geographical or emission features, 5 to 7 sectors for every sampling site are established, e.g., Scandinavia, or the centres of brown coal combustion in the former GDR. Particulary from the sectors of the former GDR, the precipitation was over-averaged contaminated anthropogenically in the years before the political change. Some components were significantly raised in comparison to other sectors. However, acidity remained on the level of the other sectors in the 80 s. In the early 90s, anthropogenic emissions were systematically reduced partly by substitution of brown coal of inferior quality, better flue gas cleaning and partly by closing down industries. The effect of such steps on the wet deposition is being studied in a national German SANA research project (SANA: scientific program of rehabilitation of the atmosphere). In this project, the sampling sites were extended to 7 while maintaining the sampling procedure and the recording of relevant meteorological input-data. As a result, there now exists a homogeneous long-term data base allowing us to study the effects of emissions on wet deposition by the rehabilitation of the atmosphere in the former GDR. The paper focusses on changes in sulphate, nitrate, calcium, acidity, chloride and potassium concentrations in precipitation at the 3 so-called long-term sites. There are conspicuous decreases of some ions on one hand, but there is also an increase of nitrate and acidity, especially in recent years

Effect of pair bond duration when included as a fixed effect in the models presented in Table 1.

<p>Estimates are presented on their original scale and reflect changes per 365 d (logit scale for binomial models, and square-root scale for models on courtship rates #20 to #22).</p><p>Bold characters in the table emphasize significance (<i>p</i> < 0.05); italic characters indicate trends (<i>p</i> < 0.10).</p><p>Underlying data for each test can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002248#pbio.1002248.s001" target="_blank">S1 Data</a>.</p